Impaired endothelial function is observed in several disease states that are related to obesity, such as atherosclerosis, coronary artery disease, and diabetes. Oxidative stress contributes to the development of these obesity-related diseases. NADPH oxidase is a major source of oxidative stress within the vasculature, and has been linked with the Metabolic Syndrome. However, there is no clear evidence that NADPH oxidase generated oxidative stress results in endothelial dysfunction in vivo. Furthermore, the mechanism(s) of exercise training-induced improvements in endothelial function have not been determined. The objectives of this study are to determine the impact of in vivo NADPH oxidase activity on endothelial function in obese as compared to lean individuals, and to determine the mechanism of training-induced improvements in endothelial function. Our unique microdialysis methodology will allow monitoring of microvascular/endothelial function and ROS generation, as well as the administration of pharmacological agents directly into muscle. The central hypothesis of this project is that elevated NADPH oxidase activity in obese individuals will contribute to microvascular endothelial dysfunction in skeletal muscle, and that endothelial function can be improved with a 12-week aerobic interval exercise intervention through an attenuation of NADPH oxidase activity.